The invention relates to a process for preparing tetrasubstituted imidazole derivatives represented by the formula (I)

wherein R1, R2, R3 and R4 are as defined in the specification below.
The compounds of formula (I) inhibit the in vitro activity of p38 in the nanomolar range. In addition, the compounds inhibit the in vitro secretion of tumor necrosis factor α (TNF-α) and IL-β in the nanomolar range. Animal models demonstrate the inhibition of LPS induces TNF-α, as well as the inhibition of rheumatoid arthritis. The compounds of formula (I) are useful in the treatment of a variety of cytokine related disorders including rheumatoid arthritis, inflammatory bowel disease, septic shock, osteoporosis, osteoarthritis, neuropathic pain, HIV replication, HIV dementia, viral myocarditis, insulin-dependent diabetes, non-insulin dependent diabetes, periodontal disease, restenosis, alopecia areta, T-cell depletion in HIV infection or AIDS, psoriasis, acute pancreatitis, allograft rejection, allergic inflammation in the lung, atherosclerosis, multiple sclerosis, cachexia, Alzheimer's disease, stroke, Crohn's disease, ischemia, congestive heart failure, pulmonary fibrosis, hepatitis, glioblastoma, Guillain-Barre Syndrome and systemic lupus erythematosus. (U.S. Pat. No. 5,965,583 Issued Oct. 12, 1999)
The current invention relates to an efficient process for preparing compounds of formula (I). In a further aspect, the present invention relates to a process for preparing the compound of formula (II).

The compound of formula (II) is an orally active inhibitor of p38 kinase. p38 kinase inhibitors have utility in suppressing the release of TNF-α from monocytes and would be expected to suppress signal transduction initiated by this proinflammatory mediator. Thus p38 kinase inhibitors have utility in the treatment of various inflammatory and autoimmune disorders such as rheumatoid arthritis, sepsis, inflammatory bowel disease, acute respiratory distress syndrome, as well as cachexia and bone resorption (osteoporosis and osteoarthritis).
The present invention further relates to novel crystalline structures of the compound of formula (II), more specifically Form A and Form B.
A process for synthesizing pyridyl imidazole compounds is disclosed in U.S. Pat. No. 5,670,527, issued Sep. 23, 1997 (Adams, J. L., et. al., SmithKline Beecham Corp. Assignee) and in PCT application WO 96/21452, published Jul., 18, 1996 (Adams, J. L., et. al., SmithKline Beecham Corporation).
U.S. Pat. No. 5,965,583 (Issued Oct. 12, 1999), which is incorporated herein by reference, disclose a process for preparing the compounds of formula (I). This process requires chromatographic separation of intermediates, making it unsuitable for large scale production.
Thus there exists a need for a process which is compatible with large scale production needs and which achieves acceptable levels of purity and yield.